Effects of stress can be passed down generations, finds rat study

A new study published in BMC Medicine suggests that the inherited epigenetic effects of stress could affect pregnancies for generations.

As well as having short pregnancies, the descendants of stressed rats also exhibited higher glucose levels and weighed less than the control group.

Researchers at the University of Lethbridge in Canada investigated how preterm births are influenced by stress using an animal model. Rats were used in these experiments as, in general, there is very little variation between rat pregnancies.

The researchers subjected one generation of rats to stress during late pregnancy. The next two generations bred from the stressed rats were then divided into "stressed" and "non-stressed" groups.

The team observed that the daughters of the rats in the stressed group had shorter pregnancies than the daughters of non-stressed rats. Unexpectedly, the granddaughters of stressed rats had shorter pregnancies regardless of whether their mothers had been stressed or not.

As well as having short pregnancies, the descendants of stressed rats also exhibited higher glucose levels and weighed less than the control group.

MicroRNA - rather than DNA signatures - responsible for these epigenetic changes

The team says that these changes are due to epigenetics. Specifically, in this case, they believe non-coding RNA molecules - microRNA - are regulating gene expression.

Senior author Gerlinde Metz says that, previously, epigenetic studies have mainly focused on DNA methylation signatures rather than microRNA. This is significant, she adds, because until now, it was not known whether microRNA could be generated by experiences and inherited across generations.

Metz says the study shows that stress across generations becomes powerful enough to induce features that are equivalent to human preterm birth. The team hopes that with further understanding of the mechanisms that generate these epigenetic signatures, it may become possible to predict and prevent preterm birth from occurring in humans.

The researchers add that the findings also have implications outside of pregnancy, as they suggest that the causes of various diseases could be rooted in the experiences of our ancestors.

"The study showed that there are changes in glucose metabolism," Metz told Medical News Today, "indicating a greater risk for diabetes among animals whose ancestors were stressed. In another study, we showed that prenatal stress in an animal model induces epigenetic signatures of human neurological and psychiatric disease, such as multiple sclerosis, depression autism."

"My feeling is that there are other conditions, such as cardiovascular disease, which may also be influenced by early and ancestral experiences," Metz added.

We asked Gerlinde Metz whether, in addition to the elevated glucose levels, smaller weight and preterm birth, the descendants of the stressed rats exhibited any behavioral differences when compared with the control group rats.

Metz replied:

"The offspring of stressed rat mothers showed delayed sensorimotor development and delayed physical development. For example, the offspring took longer to respond to being placed on an inclined plane. Normally, a young rat would turn around quickly when being placed facing down the incline, and then walk towards the top of the inclined plane. Offspring from a stressed mother did not respond that quickly.

When growing up, the pregnant daughters of stressed mothers also showed behavioral changes in their maternal behavior. From our other studies we know that behavioral changes induced by prenatal and ancestral stress will last a lifetime."

This study found that a stress-response gene - called corticotropin releasing factor type 1 - showed increased expression not only in stressed female rats, but also in their offspring at birth.

The researchers in this study also observed behavioral differences in the offspring of stressed rats, compared with the offspring of rats from a control group.

As psychiatric illnesses such as post-traumatic stress disorder and schizophrenia are associated with stress, the Israeli team suggests that a clearer understanding of the mechanisms involved could improve diagnostics and treatment for these conditions.

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